目的 评价生脉注射液对细胞色素P450（cytochrome P450，CYP450）酶与转运体活性的影响。方法 根据美国食品和药品管理局（FDA）发布的《药物相互作用研究指导原则（2017）》以及我国发布的《药物相互作用研究技术指导原则（试行）》，在有无生脉注射液的人肝微粒体、人源多药耐药蛋白1（multidrug resistance proteins 1，MDR1）、乳腺癌耐药蛋白（breast cancer resistance protein，BCRP）囊泡和人胚胎肾细胞HEK293中，培养CYP450酶与转运体的探针底物，采用液相色谱-串联质谱联用（LC-MS/MS）及酶标仪检测探针底物代谢产物的生成量或探针底物量，并计算半数抑制浓度（50% concentration of inhibition，IC₅₀）值。结果 在30%（体积分数）浓度范围内，生脉注射液对CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A4的活性均具有抑制作用，其IC₅₀值分别为6.12%、2.72%、10.00%～30.00%、14.31%、12.96%、12.26%、3.72%。生脉注射液对转运体MDR1、BCRP以及有机阴离子1B1（organic anion transporting polypeptide 1B1，OATP1B1）的活性也具有抑制作用，其IC₅₀值分别为0.15%、0.75%、2.03%。结论 生脉注射液可以影响CYP450酶以及转运体活性，与转运体MDR1与BCRP底物联用时，发生药物相互作用的风险较大，临床联用时需监测相关指标或谨慎联用。

Objective To evaluate the effect of Shengmai Injection (生脉注射液) on activity of cytochrome P450 (CYP450) enzymes and transporters. Methods According to “Guiding Principles for Drug Interaction Research (2017)” issued by US Food and Drug Administration (FDA) and “Technical Guidelines for Drug Interaction Research (Trial)” issued by China, CYP450 enzyme and transporter probe substrate were cultured in human liver microsomes and human multidrug resistance proteins 1 (MDR1), breast cancer resistance protein (BCRP) vesicles and human embryonic kidney cells HEK293 with or without Shengmai Injection; Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and microplate reader were used to detect amount of probe substrate metabolites or probe substrate, and 50% concentration of inhibition (IC₅₀) value was calculated. Results Within concentration range of 30% (volume percentage), Shengmai Injection had an inhibitory effect on activities of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, with IC₅₀ values of 6.12%, 2.72%, 10.00%—30.00%. 14.31%, 12.96%, 12.26%, and 3.72%. Shengmai Injection also had the inhibitory effects on activities of transporters MDR1, BCRP and organic anion transporting polypeptide 1B1 (OATP1B1), with IC₅₀ values of 0.15%, 0.75% and 2.03%. Conclusion Shengmai Injection can affect the activity of CYP450 enzymes and transporters. When combined with transporter MDR1 and BCRP substrate, there is a greater risk of drug interactions. It is necessary to monitor related indicators or use caution in combination in clinical combined use.

R285.62

国家自然科学基金面上项目（81573647）；国家自然科学基金面上项目（82074222）；国家自然科学基金青年科学基金项目（81803887）；上海市科学技术委员会重点实验室建设（医疗类）项目（14DZ2273200）；上海市科学技术委员会引导类项目（19401934300）；上海市卫生和计划生育委员会中医药事业发展三年行动计划项目[ZY（2018-2020）-CCCX-2003-07]；上海市临床重点专科（中医心病科）项目（shslczdzk05301）